search
Back to results

Evaluating the Safety and Efficacy of the VRC01 Antibody in Reducing Acquisition of HIV-1 Infection in Women

Primary Purpose

HIV Infections

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
VRC01
Placebo for VRC01
Sponsored by
National Institute of Allergy and Infectious Diseases (NIAID)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for HIV Infections focused on measuring HIV-1 Infections

Eligibility Criteria

18 Years - 50 Years (Adult)FemaleAccepts Healthy Volunteers

Inclusion Criteria:

General and Demographic Criteria

  • Age of 18 to 50 years
  • Access to a participating clinical research site (CRS) and willingness to be followed for the planned duration of the study
  • Ability and willingness to provide informed consent
  • Assessment of understanding: volunteer demonstrates understanding of this study and completes a questionnaire prior to first infusion with verbal demonstration of understanding of all questionnaire items answered incorrectly
  • Agrees not to enroll in another study of an investigational research agent for the duration of the participant's trial participation
  • Good general health as shown by medical history, physical exam, and screening laboratory tests

HIV-Related Criteria

  • Willingness to receive HIV test results
  • Willingness to discuss HIV infection risks and amenable to HIV risk reduction counseling
  • Persons born Female (assigned female sex at birth) and identifying as a female, who, in the 6 months prior to randomization, has had vaginal and/or anal intercourse with a male partner
  • All volunteers who have been in a monogamous relationship with an HIV-1 seronegative partner for greater than 1 year are excluded.

Laboratory Inclusion Values+

Hematology

  • Hemoglobin (Hgb) greater than or equal to 10.5 g/dL for volunteers who were born female, greater than or equal to 13.0 g/dL for volunteers who were born male
  • Platelets greater than or equal to 100,000 cells/mm^3

Chemistry

  • Alanine aminotransferase (ALT) less than 2.5 times the institutional upper limit of normal and creatinine less than or equal to 1.25 times the institutional upper limit of normal

Virology

  • HIV uninfected, as defined in the study specific procedures (SSP), within 30 days prior to enrollment

Urine

  • Negative, trace, or 1+ urine protein by dipstick

Reproductive Status

  • Volunteers capable of becoming pregnant: negative serum or urine beta human chorionic gonadotropin (β-HCG) pregnancy test performed at the screening visit and prior to infusion on the day of initial infusion. Persons who are NOT capable of becoming pregnant due to having undergone total hysterectomy or bilateral oophorectomy (verified by medical records) are not required to undergo pregnancy testing.
  • Reproductive status: A volunteer who is capable of becoming pregnant must agree to consistently use effective contraception (see the protocol and SSP for more information) for sexual activity that could lead to pregnancy from at least 21 days prior to enrollment through the last required protocol clinic visit.
  • Volunteers capable of becoming pregnant must also agree not to seek pregnancy through alternative methods, such as artificial insemination or in vitro fertilization until after the last required protocol clinic visit

Exclusion Criteria:

General

  • Investigational research agents received within 30 days before first infusion
  • Body mass index (BMI) greater than or equal to 40
  • Pregnant or breastfeeding
  • Any reactive, indeterminate, or positive HIV test, even if subsequent testing indicates that the individual is not HIV infected.

Monoclonal antibodies and vaccines

  • Previous receipt of humanized or human monoclonal antibodies (mAbs), whether licensed or investigational
  • HIV vaccine(s) received in a prior HIV vaccine trial. For volunteers who have received control/placebo in an HIV vaccine trial, the HVTN 703/HPTN 081 Protocol Safety Review Team (PSRT) will determine eligibility on a case-by-case basis.

Immune System

  • Serious adverse reactions to VRC01 formulation components such as sodium citrate, sodium chloride, and L-arginine hydrochloride, including history of anaphylaxis and related symptoms such as hives, respiratory difficulty, angioedema, and/or abdominal pain.
  • Autoimmune disease, including Type I diabetes mellitus (Not excluded from participation: Volunteer with mild, stable and uncomplicated autoimmune disease that does not require consistent immunosuppressive medication and that, in the judgment of the site investigator, is likely not subject to exacerbation and likely not to complicate reactogenicity and adverse event (AE) assessments)
  • Immunodeficiency syndrome

Clinically significant medical conditions

  • Clinically significant medical condition, physical examination findings, clinically significant abnormal laboratory results, or past medical history with clinically significant implications for current health. A clinically significant condition or process includes but is not limited to:

    • Any contraindication to repeated infusions or blood draws, including inability to establish venous access;
    • A condition that requires active medical intervention or monitoring to avert grave danger to the volunteer's health or well-being during the study period; or
    • A condition or process for which signs or symptoms could be confused with reactions to VRC01.
  • Any medical, psychiatric, occupational, or other condition that, in the judgment of the investigator, would interfere with, or serve as a contraindication to, protocol adherence, assessment of safety or infusion reactions, or a volunteer's ability to give informed consent
  • Psychiatric condition that precludes compliance with the protocol. Specifically excluded are persons with psychoses within the past 3 years, ongoing risk for suicide, or history of suicide attempt or gesture within the past 3 years.
  • Asthma, other than mild, well-controlled asthma
  • Bleeding disorder diagnosed by a doctor (e.g., factor deficiency, coagulopathy, or platelet disorder requiring special precautions)
  • Malignancy (Not excluded from participation: Volunteer who has had malignancy excised surgically and who, in the investigator's estimation, has a reasonable assurance of sustained cure. or who is unlikely to experience recurrence of malignancy during the period of the study)
  • Seizure disorder: History of seizure(s) within past three years. Also exclude if volunteer has used medications in order to prevent or treat seizure(s) at any time within the past 3 years.
  • History of hereditary angioedema, acquired angioedema, or idiopathic angioedema
  • History of organ or tissue transplantation
  • Known hepatic or renal dysfunction

Sites / Locations

  • Gaborone CRS
  • Kisumu Crs
  • Blantyre CRS
  • Malawi CRS
  • Polana Canico Health Research and Training Center (CISPOC), National Institute of Health (INS) CRS
  • The Aurum Institute Tembisa Clinical Research Centre CRS
  • Soweto HVTN CRS
  • Ward 21 CRS
  • Wits Reproductive Health and HIV Institute CRS (WRHI CRS)
  • Synexus Stanza Clinical Research Centre CRS
  • Botha's Hill CRS
  • Chatsworth CRS
  • CAPRISA eThekwini CRS
  • Vulindlela CRS
  • Aurum Institute Klerksdorp CRS
  • Rustenburg CRS
  • Groote Schuur HIV CRS
  • National Institute for Medical Research (NIMR) - Mbeya Medical Research Center (MMRC) Network CRS
  • Seke South CRS
  • Milton Park CRS
  • Spilhaus CRS

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Placebo Comparator

Arm Label

Group 1: Low-Dose VRC01

Group 2: High-Dose VRC01

Group 3: Placebo for VRC01

Arm Description

Participants will receive an IV infusion of 10 mg/kg of VRC01 over about 30 to 60 minutes at Weeks 0, 8, 16, 24, 32, 40, 48, 56, 64, and 72.

Participants will receive an IV infusion of 30 mg/kg of VRC01 over about 30 to 60 minutes at Weeks 0, 8, 16, 24, 32, 40, 48, 56, 64, and 72.

Participants will receive an IV infusion of placebo for VRC01 over about 30 to 60 minutes at Weeks 0, 8, 16, 24, 32, 40, 48, 56, 64, and 72.

Outcomes

Primary Outcome Measures

Number of Participants Reporting Local Reactogenicity Signs and Symptoms: Pain and/or Tenderness
Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 [July 2017]. The maximum grade observed for each symptom over the time frame is presented
Number of Participants Reporting Local Reactogenicity Signs and Symptoms: Erythema and/or Induration
Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 [July 2017]. The maximum grade observed for each symptom over the time frame is presented
Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms
Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 [July 2017]. The following symptoms are considered as systemic reactogenicity if the onset date was within the periods of assessment specified in the protocol: malaise and/or fatigue, myalgia, headache, nausea, vomiting, chills, arthralgia, and body temperature. The item Max. Systemic Symptoms is the maximum of the individual systemic reactogenicities excluding body temperature for a participant.
Chemistry and Hematology Laboratory Measures - Alanine Aminotransferase (ALT)
For each local laboratory measure, summary statistics are presented by treatment group and timepoint.
Chemistry and Hematology Laboratory Measures - Creatinine
For each local laboratory measure, summary statistics are presented by treatment group and timepoint.
Chemistry and Hematology Laboratory Measures - Hemoglobin
For each local laboratory measure, summary statistics are presented by treatment group and timepoint.
Chemistry and Hematology Laboratory Measures - Lymphocyte Count, Neutrophil Count
For each local laboratory measure, summary statistics are presented by treatment group and timepoint.
Chemistry and Hematology Laboratory Measures - Platelets, White Blood Cells (WBC)
For each local laboratory measure, summary statistics are presented by treatment group and timepoint.
Chemistry and Hematology Laboratory Measures Meeting Grade 3 AE Criteria or Above
The number (percentage) of participants with chemistry and hematology laboratory measures meeting grade 3 AE criteria or above as specified in the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 [July 2017] is tabulated by treatment group and timepoint. Excludes measures taken prior to exposure to study product at Week 0/Infusion 1.
Number of Participants With Early Infusion Discontinuation and Reasons for Discontinuation
The number (percentage) of participants with early permanent discontinuation of infusions and their reason for discontinuation is summarized by treatment group. Includes all discontinuations documented on a study case report form.
Incidence Rate of Early Infusion Discontinuation
Incidence rate (95% CI) of early infusion discontinuation per 100 person years. Includes discontinuations documented on a study case report form and operational discontinuations defined as 20 consecutive weeks without participant contact. Discontinuations due to pregnancy, death, or HIV-1 infection are right-censored.
Number of Participants With Documented HIV-1 Infection by the Week 80 Visit
Prevention efficacy (PE) is measured as 1 minus the ratio (VRC01:control) of cumulative incidences of HIV-1 infection diagnosis between enrollment and the week 80 visit for assessment of the primary efficacy end point. Cumulative incidence was estimated with the Nelson-Aalen estimator for the cumulative hazard function, with stratification according to VRC01 dose and trial.

Secondary Outcome Measures

Serum Concentration of VRC01 in Participants Assigned to Receive the mAb
The pharmacokinetic analyses of VRC01 involved a subgroup of VRC01 recipients who had not acquired HIV-1 infection through the week 88 visit and were not likely to have used preexposure prophylaxis (on the basis of self-report or testing of dried blood-spot samples), randomly sampled among the trials and dose groups. Midpoint and trough concentrations are the participant-level median concentrations at the 4-week and 8-week postinfusion visits, respectively, across all 10 infusion intervals.
VRC01 Clinical Lot Neutralization of Founder Viruses (IC80)
The VRC01 80% inhibitory concentration (IC80) of acquired isolates was measured with the TZM-bl assay using the earliest available post-HIV-infection serum sample. Median and IQR are summarized immediately below, then the analysis of prevention efficacy was repeated for each of three prespecified categories of in vitro susceptibility of the infecting strain (IC80 less than 1 μg per milliliter, 1 to 3 μg per milliliter, or >3 μg per milliliter) with the use of the Aalen-Johansen estimator.
VRC01 Serum Neutralization of Autologous Founder Viruses (ID50, ID80)
Autologous titer (ID50, ID80) summaries, based on most sensitive virus, for first RNA+ samples from a subset of HIV-infected VRC01 recipients. Values below the limit of detection (less than 10) were set to NA. Summaries are only computed for the Pooled VRC01 arm.

Full Information

First Posted
October 1, 2015
Last Updated
February 8, 2022
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
search

1. Study Identification

Unique Protocol Identification Number
NCT02568215
Brief Title
Evaluating the Safety and Efficacy of the VRC01 Antibody in Reducing Acquisition of HIV-1 Infection in Women
Official Title
A Phase 2b Study to Evaluate the Safety and Efficacy of VRC01 Broadly Neutralizing Monoclonal Antibody in Reducing Acquisition of HIV-1 Infection in Women in Sub-Saharan Africa
Study Type
Interventional

2. Study Status

Record Verification Date
February 2022
Overall Recruitment Status
Completed
Study Start Date
May 2016 (Actual)
Primary Completion Date
March 3, 2021 (Actual)
Study Completion Date
March 3, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This study will evaluate the safety and efficacy of the human monoclonal antibody (mAb) VRC-HIVMAB060-00-AB (VRC01) in preventing HIV-1 infection in high-risk, HIV-uninfected women.
Detailed Description
This study will evaluate the safety, tolerability, and efficacy of the VRC01 antibody in preventing HIV-1 infection in healthy women at high risk of HIV infection. Participants will be enrolled from a cohort of heterosexual women in sub-Saharan Africa. An equal number of study participants will be randomized to receive VRC01 mAb by IV infusion at a dose of 10 mg/kg or 30 mg/kg every 8 weeks, or to receive control infusions every 8 weeks. All participants will receive the VRC01 antibody or placebo by intravenous infusion at Weeks 0 (study entry), 8, 16, 24, 32, 40, 48, 56, 64, and 72. For 3 days following each infusion, participants will be asked to record and report any symptoms to study researchers. In addition to the infusion visits, participants will attend study visits at Weeks 4, 8 + 5 days, 12, 20, 28, 36, 44, 52, 60, 68, 76, 80, 84, 88, and 92. All study visits will include blood collection and HIV testing and counseling. Select study visits will include a medical history review, physical exam, urine collection, pregnancy testing for participants capable of becoming pregnant, risk reduction counseling, and an interview/questionnaire.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infections
Keywords
HIV-1 Infections

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
1924 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Group 1: Low-Dose VRC01
Arm Type
Experimental
Arm Description
Participants will receive an IV infusion of 10 mg/kg of VRC01 over about 30 to 60 minutes at Weeks 0, 8, 16, 24, 32, 40, 48, 56, 64, and 72.
Arm Title
Group 2: High-Dose VRC01
Arm Type
Experimental
Arm Description
Participants will receive an IV infusion of 30 mg/kg of VRC01 over about 30 to 60 minutes at Weeks 0, 8, 16, 24, 32, 40, 48, 56, 64, and 72.
Arm Title
Group 3: Placebo for VRC01
Arm Type
Placebo Comparator
Arm Description
Participants will receive an IV infusion of placebo for VRC01 over about 30 to 60 minutes at Weeks 0, 8, 16, 24, 32, 40, 48, 56, 64, and 72.
Intervention Type
Biological
Intervention Name(s)
VRC01
Other Intervention Name(s)
Human monoclonal antibody (mAb) VRC-HIVMAB060-00-AB
Intervention Description
Administered by IV infusion; total dose will vary based on participant's weight
Intervention Type
Biological
Intervention Name(s)
Placebo for VRC01
Intervention Description
Sodium Chloride for Injection USP, 0.9%; administered by IV infusion
Primary Outcome Measure Information:
Title
Number of Participants Reporting Local Reactogenicity Signs and Symptoms: Pain and/or Tenderness
Description
Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 [July 2017]. The maximum grade observed for each symptom over the time frame is presented
Time Frame
Measured through 3 days after each infusion at Weeks 0, 8, 16, 24, 32, 40, 48, 56, 64, 72.
Title
Number of Participants Reporting Local Reactogenicity Signs and Symptoms: Erythema and/or Induration
Description
Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 [July 2017]. The maximum grade observed for each symptom over the time frame is presented
Time Frame
Measured through 3 days after each infusion at Weeks 0, 8, 16, 24, 32, 40, 48, 56, 64, 72.
Title
Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms
Description
Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 [July 2017]. The following symptoms are considered as systemic reactogenicity if the onset date was within the periods of assessment specified in the protocol: malaise and/or fatigue, myalgia, headache, nausea, vomiting, chills, arthralgia, and body temperature. The item Max. Systemic Symptoms is the maximum of the individual systemic reactogenicities excluding body temperature for a participant.
Time Frame
Measured through 3 days after each infusion at Weeks 0, 8, 16, 24, 32, 40, 48, 56, 64, 72.
Title
Chemistry and Hematology Laboratory Measures - Alanine Aminotransferase (ALT)
Description
For each local laboratory measure, summary statistics are presented by treatment group and timepoint.
Time Frame
Measured at Weeks 0, 8, 16, 24, 32, 40, 48, 56, 64, 72.
Title
Chemistry and Hematology Laboratory Measures - Creatinine
Description
For each local laboratory measure, summary statistics are presented by treatment group and timepoint.
Time Frame
Measured at Weeks 0, 8, 16, 24, 32, 40, 48, 56, 64, 72.
Title
Chemistry and Hematology Laboratory Measures - Hemoglobin
Description
For each local laboratory measure, summary statistics are presented by treatment group and timepoint.
Time Frame
Measured at Weeks 0, 8, 16, 24, 32, 40, 48, 56, 64, 72.
Title
Chemistry and Hematology Laboratory Measures - Lymphocyte Count, Neutrophil Count
Description
For each local laboratory measure, summary statistics are presented by treatment group and timepoint.
Time Frame
Measured at Weeks 0, 8, 16, 24, 32, 40, 48, 56, 64, 72.
Title
Chemistry and Hematology Laboratory Measures - Platelets, White Blood Cells (WBC)
Description
For each local laboratory measure, summary statistics are presented by treatment group and timepoint.
Time Frame
Measured at Weeks 0, 8, 16, 24, 32, 40, 48, 56, 64, 72.
Title
Chemistry and Hematology Laboratory Measures Meeting Grade 3 AE Criteria or Above
Description
The number (percentage) of participants with chemistry and hematology laboratory measures meeting grade 3 AE criteria or above as specified in the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 [July 2017] is tabulated by treatment group and timepoint. Excludes measures taken prior to exposure to study product at Week 0/Infusion 1.
Time Frame
Measured at Weeks 8, 16, 24, 32, 40, 48, 56, 64, 72.
Title
Number of Participants With Early Infusion Discontinuation and Reasons for Discontinuation
Description
The number (percentage) of participants with early permanent discontinuation of infusions and their reason for discontinuation is summarized by treatment group. Includes all discontinuations documented on a study case report form.
Time Frame
Measured through Week 72 (the last infusion visit).
Title
Incidence Rate of Early Infusion Discontinuation
Description
Incidence rate (95% CI) of early infusion discontinuation per 100 person years. Includes discontinuations documented on a study case report form and operational discontinuations defined as 20 consecutive weeks without participant contact. Discontinuations due to pregnancy, death, or HIV-1 infection are right-censored.
Time Frame
Measured through Week 72 (the last infusion visit).
Title
Number of Participants With Documented HIV-1 Infection by the Week 80 Visit
Description
Prevention efficacy (PE) is measured as 1 minus the ratio (VRC01:control) of cumulative incidences of HIV-1 infection diagnosis between enrollment and the week 80 visit for assessment of the primary efficacy end point. Cumulative incidence was estimated with the Nelson-Aalen estimator for the cumulative hazard function, with stratification according to VRC01 dose and trial.
Time Frame
Measured through Week 80.
Secondary Outcome Measure Information:
Title
Serum Concentration of VRC01 in Participants Assigned to Receive the mAb
Description
The pharmacokinetic analyses of VRC01 involved a subgroup of VRC01 recipients who had not acquired HIV-1 infection through the week 88 visit and were not likely to have used preexposure prophylaxis (on the basis of self-report or testing of dried blood-spot samples), randomly sampled among the trials and dose groups. Midpoint and trough concentrations are the participant-level median concentrations at the 4-week and 8-week postinfusion visits, respectively, across all 10 infusion intervals.
Time Frame
Day 61 (5 days post infusion #2), Midpoint (4-weeks post infusion visits): Weeks 4, 12, 16, 28, 36, 44, 52, 60, 68, 76 and Trough (infusion visits): Pre dose at Weeks 0 (study entry), 8, 16, 24, 32, 40, 48, 56, 64, and 72.
Title
VRC01 Clinical Lot Neutralization of Founder Viruses (IC80)
Description
The VRC01 80% inhibitory concentration (IC80) of acquired isolates was measured with the TZM-bl assay using the earliest available post-HIV-infection serum sample. Median and IQR are summarized immediately below, then the analysis of prevention efficacy was repeated for each of three prespecified categories of in vitro susceptibility of the infecting strain (IC80 less than 1 μg per milliliter, 1 to 3 μg per milliliter, or >3 μg per milliliter) with the use of the Aalen-Johansen estimator.
Time Frame
Measured through Week 80.
Title
VRC01 Serum Neutralization of Autologous Founder Viruses (ID50, ID80)
Description
Autologous titer (ID50, ID80) summaries, based on most sensitive virus, for first RNA+ samples from a subset of HIV-infected VRC01 recipients. Values below the limit of detection (less than 10) were set to NA. Summaries are only computed for the Pooled VRC01 arm.
Time Frame
First RNA+ Sample detected from baseline up to Week 104.

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: General and Demographic Criteria Age of 18 to 50 years Access to a participating clinical research site (CRS) and willingness to be followed for the planned duration of the study Ability and willingness to provide informed consent Assessment of understanding: volunteer demonstrates understanding of this study and completes a questionnaire prior to first infusion with verbal demonstration of understanding of all questionnaire items answered incorrectly Agrees not to enroll in another study of an investigational research agent for the duration of the participant's trial participation Good general health as shown by medical history, physical exam, and screening laboratory tests HIV-Related Criteria Willingness to receive HIV test results Willingness to discuss HIV infection risks and amenable to HIV risk reduction counseling Persons born Female (assigned female sex at birth) and identifying as a female, who, in the 6 months prior to randomization, has had vaginal and/or anal intercourse with a male partner All volunteers who have been in a monogamous relationship with an HIV-1 seronegative partner for greater than 1 year are excluded. Laboratory Inclusion Values+ Hematology Hemoglobin (Hgb) greater than or equal to 10.5 g/dL for volunteers who were born female, greater than or equal to 13.0 g/dL for volunteers who were born male Platelets greater than or equal to 100,000 cells/mm^3 Chemistry Alanine aminotransferase (ALT) less than 2.5 times the institutional upper limit of normal and creatinine less than or equal to 1.25 times the institutional upper limit of normal Virology HIV uninfected, as defined in the study specific procedures (SSP), within 30 days prior to enrollment Urine Negative, trace, or 1+ urine protein by dipstick Reproductive Status Volunteers capable of becoming pregnant: negative serum or urine beta human chorionic gonadotropin (β-HCG) pregnancy test performed at the screening visit and prior to infusion on the day of initial infusion. Persons who are NOT capable of becoming pregnant due to having undergone total hysterectomy or bilateral oophorectomy (verified by medical records) are not required to undergo pregnancy testing. Reproductive status: A volunteer who is capable of becoming pregnant must agree to consistently use effective contraception (see the protocol and SSP for more information) for sexual activity that could lead to pregnancy from at least 21 days prior to enrollment through the last required protocol clinic visit. Volunteers capable of becoming pregnant must also agree not to seek pregnancy through alternative methods, such as artificial insemination or in vitro fertilization until after the last required protocol clinic visit Exclusion Criteria: General Investigational research agents received within 30 days before first infusion Body mass index (BMI) greater than or equal to 40 Pregnant or breastfeeding Any reactive, indeterminate, or positive HIV test, even if subsequent testing indicates that the individual is not HIV infected. Monoclonal antibodies and vaccines Previous receipt of humanized or human monoclonal antibodies (mAbs), whether licensed or investigational HIV vaccine(s) received in a prior HIV vaccine trial. For volunteers who have received control/placebo in an HIV vaccine trial, the HVTN 703/HPTN 081 Protocol Safety Review Team (PSRT) will determine eligibility on a case-by-case basis. Immune System Serious adverse reactions to VRC01 formulation components such as sodium citrate, sodium chloride, and L-arginine hydrochloride, including history of anaphylaxis and related symptoms such as hives, respiratory difficulty, angioedema, and/or abdominal pain. Autoimmune disease, including Type I diabetes mellitus (Not excluded from participation: Volunteer with mild, stable and uncomplicated autoimmune disease that does not require consistent immunosuppressive medication and that, in the judgment of the site investigator, is likely not subject to exacerbation and likely not to complicate reactogenicity and adverse event (AE) assessments) Immunodeficiency syndrome Clinically significant medical conditions Clinically significant medical condition, physical examination findings, clinically significant abnormal laboratory results, or past medical history with clinically significant implications for current health. A clinically significant condition or process includes but is not limited to: Any contraindication to repeated infusions or blood draws, including inability to establish venous access; A condition that requires active medical intervention or monitoring to avert grave danger to the volunteer's health or well-being during the study period; or A condition or process for which signs or symptoms could be confused with reactions to VRC01. Any medical, psychiatric, occupational, or other condition that, in the judgment of the investigator, would interfere with, or serve as a contraindication to, protocol adherence, assessment of safety or infusion reactions, or a volunteer's ability to give informed consent Psychiatric condition that precludes compliance with the protocol. Specifically excluded are persons with psychoses within the past 3 years, ongoing risk for suicide, or history of suicide attempt or gesture within the past 3 years. Asthma, other than mild, well-controlled asthma Bleeding disorder diagnosed by a doctor (e.g., factor deficiency, coagulopathy, or platelet disorder requiring special precautions) Malignancy (Not excluded from participation: Volunteer who has had malignancy excised surgically and who, in the investigator's estimation, has a reasonable assurance of sustained cure. or who is unlikely to experience recurrence of malignancy during the period of the study) Seizure disorder: History of seizure(s) within past three years. Also exclude if volunteer has used medications in order to prevent or treat seizure(s) at any time within the past 3 years. History of hereditary angioedema, acquired angioedema, or idiopathic angioedema History of organ or tissue transplantation Known hepatic or renal dysfunction
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lawrence Corey
Organizational Affiliation
HVTN; FHCRC
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Myron Cohen
Organizational Affiliation
HPTN; University of North Carolina
Official's Role
Study Chair
Facility Information:
Facility Name
Gaborone CRS
City
Gaborone
State/Province
South-East District
Country
Botswana
Facility Name
Kisumu Crs
City
Kisumu
State/Province
Nyanza
ZIP/Postal Code
40100
Country
Kenya
Facility Name
Blantyre CRS
City
Blantyre
State/Province
Southern Region
Country
Malawi
Facility Name
Malawi CRS
City
Lilongwe
Country
Malawi
Facility Name
Polana Canico Health Research and Training Center (CISPOC), National Institute of Health (INS) CRS
City
Maputo
Country
Mozambique
Facility Name
The Aurum Institute Tembisa Clinical Research Centre CRS
City
Johannesburg
State/Province
Gauteng
ZIP/Postal Code
1632
Country
South Africa
Facility Name
Soweto HVTN CRS
City
Johannesburg
State/Province
Gauteng
ZIP/Postal Code
1862
Country
South Africa
Facility Name
Ward 21 CRS
City
Johannesburg
State/Province
Gauteng
ZIP/Postal Code
2001
Country
South Africa
Facility Name
Wits Reproductive Health and HIV Institute CRS (WRHI CRS)
City
Johannesburg
State/Province
Gauteng
ZIP/Postal Code
2038
Country
South Africa
Facility Name
Synexus Stanza Clinical Research Centre CRS
City
Pretoria
State/Province
Gauteng
ZIP/Postal Code
0122
Country
South Africa
Facility Name
Botha's Hill CRS
City
Durban
State/Province
Kwa Zulu Natal
ZIP/Postal Code
3660
Country
South Africa
Facility Name
Chatsworth CRS
City
Chatsworth
State/Province
KwaZulu-Natal
ZIP/Postal Code
4030
Country
South Africa
Facility Name
CAPRISA eThekwini CRS
City
Durban
State/Province
KwaZulu-Natal
ZIP/Postal Code
4013
Country
South Africa
Facility Name
Vulindlela CRS
City
Durban
State/Province
KwaZulu-Natal
ZIP/Postal Code
4013
Country
South Africa
Facility Name
Aurum Institute Klerksdorp CRS
City
Klerksdorp
State/Province
North West Province
ZIP/Postal Code
2571
Country
South Africa
Facility Name
Rustenburg CRS
City
Rustenburg
State/Province
North West Province
ZIP/Postal Code
0300
Country
South Africa
Facility Name
Groote Schuur HIV CRS
City
Cape Town
State/Province
Western Cape Province
ZIP/Postal Code
7925
Country
South Africa
Facility Name
National Institute for Medical Research (NIMR) - Mbeya Medical Research Center (MMRC) Network CRS
City
Mbeya
Country
Tanzania
Facility Name
Seke South CRS
City
Chitungwiza
Country
Zimbabwe
Facility Name
Milton Park CRS
City
Harare
Country
Zimbabwe
Facility Name
Spilhaus CRS
City
Harare
Country
Zimbabwe

12. IPD Sharing Statement

Citations:
PubMed Identifier
33587505
Citation
Edupuganti S, Mgodi N, Karuna ST, Andrew P, Rudnicki E, Kochar N, deCamp A, De La Grecca R, Anderson M, Karg C, Tindale I, Greene E, Broder GB, Lucas J, Hural J, Gallardo-Cartagena JA, Gonzales P, Frank I, Sobieszczyk M, Gomez Lorenzo MM, Burns D, Anderson PL, Miner MD, Ledgerwood J, Mascola JR, Gilbert PB, Cohen MS, Corey L; HVTN 704/HPTN 085 study group. Feasibility and Successful Enrollment in a Proof-of-Concept HIV Prevention Trial of VRC01, a Broadly Neutralizing HIV-1 Monoclonal Antibody. J Acquir Immune Defic Syndr. 2021 May 1;87(1):671-679. doi: 10.1097/QAI.0000000000002639.
Results Reference
result
PubMed Identifier
33587510
Citation
Mgodi NM, Takuva S, Edupuganti S, Karuna S, Andrew P, Lazarus E, Garnett P, Shava E, Mukwekwerere PG, Kochar N, Marshall K, Rudnicki E, Juraska M, Anderson M, Karg C, Tindale I, Greene E, Luthuli N, Baepanye K, Hural J, Gomez Lorenzo MM, Burns D, Miner MD, Ledgerwood J, Mascola JR, Donnell D, Cohen MS, Corey L; HVTN 703/HPTN 081 Team. A Phase 2b Study to Evaluate the Safety and Efficacy of VRC01 Broadly Neutralizing Monoclonal Antibody in Reducing Acquisition of HIV-1 Infection in Women in Sub-Saharan Africa: Baseline Findings. J Acquir Immune Defic Syndr. 2021 May 1;87(1):680-687. doi: 10.1097/QAI.0000000000002649.
Results Reference
result
PubMed Identifier
33493795
Citation
Huang Y, Naidoo L, Zhang L, Carpp LN, Rudnicki E, Randhawa A, Gonzales P, McDermott A, Ledgerwood J, Lorenzo MMG, Burns D, DeCamp A, Juraska M, Mascola J, Edupuganti S, Mgodi N, Cohen M, Corey L, Andrew P, Karuna S, Gilbert PB, Mngadi K, Lazarus E. Pharmacokinetics and predicted neutralisation coverage of VRC01 in HIV-uninfected participants of the Antibody Mediated Prevention (AMP) trials. EBioMedicine. 2021 Feb;64:103203. doi: 10.1016/j.ebiom.2020.103203. Epub 2021 Jan 23.
Results Reference
result
PubMed Identifier
34213402
Citation
Huang Y, Zhang L, Eaton A, Mkhize NN, Carpp LN, Rudnicki E, DeCamp A, Juraska M, Randhawa A, McDermott A, Ledgerwood J, Andrew P, Karuna S, Edupuganti S, Mgodi N, Cohen M, Corey L, Mascola J, Gilbert PB, Morris L, Montefiori DC. Prediction of serum HIV-1 neutralization titers of VRC01 in HIV-uninfected Antibody Mediated Prevention (AMP) trial participants. Hum Vaccin Immunother. 2022 Dec 31;18(1):1908030. doi: 10.1080/21645515.2021.1908030. Epub 2021 Jul 2.
Results Reference
result
PubMed Identifier
33730454
Citation
Corey L, Gilbert PB, Juraska M, Montefiori DC, Morris L, Karuna ST, Edupuganti S, Mgodi NM, deCamp AC, Rudnicki E, Huang Y, Gonzales P, Cabello R, Orrell C, Lama JR, Laher F, Lazarus EM, Sanchez J, Frank I, Hinojosa J, Sobieszczyk ME, Marshall KE, Mukwekwerere PG, Makhema J, Baden LR, Mullins JI, Williamson C, Hural J, McElrath MJ, Bentley C, Takuva S, Gomez Lorenzo MM, Burns DN, Espy N, Randhawa AK, Kochar N, Piwowar-Manning E, Donnell DJ, Sista N, Andrew P, Kublin JG, Gray G, Ledgerwood JE, Mascola JR, Cohen MS; HVTN 704/HPTN 085 and HVTN 703/HPTN 081 Study Teams. Two Randomized Trials of Neutralizing Antibodies to Prevent HIV-1 Acquisition. N Engl J Med. 2021 Mar 18;384(11):1003-1014. doi: 10.1056/NEJMoa2031738.
Results Reference
result
PubMed Identifier
34895272
Citation
Hanass-Hancock J, Carpenter B, Reddy T, Nzuza A, Gaffoor Z, Goga A, Andrasik M. Participants' characteristics and motivations to screen for HIV vaccine and monoclonal antibody trials in KwaZulu-Natal, South Africa. Trials. 2021 Dec 11;22(1):897. doi: 10.1186/s13063-021-05792-7.
Results Reference
derived

Learn more about this trial

Evaluating the Safety and Efficacy of the VRC01 Antibody in Reducing Acquisition of HIV-1 Infection in Women

We'll reach out to this number within 24 hrs